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Signaling factor interaction affecting Shh, Wnt, and BMP expression during pattern formation in the developimg limb

Research Project

Project/Area Number 13680813
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionKAWASAKI MEDICAL SCHOOL

Principal Investigator

NOHNO Tsutomu  Kawasaki Medical School, Molecular Biology, Associate Professor, 医学部, 助教授 (20098619)

Co-Investigator(Kenkyū-buntansha) NARITA Tomohiro  Kawasaki Medical School, Molecular Biology, Research Associate, 医学部, 助手 (40330550)
WADA Naoyuki  Kawasaki Medical School, Molecular Biology, Research Associate, 医学部, 助手 (50267449)
NISHIMATSU Shin-ichiro  Kawasaki Medical School, Molecular Biology, Assistant Professor, 医学部, 講師 (20222185)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsSonic hedgehog / FGF4 / Ephrin-A2 / Apical ectodermal ridge / Wnt family / Chondrogenesis / Myogenesis / Limb development / Sfrpファミリー / 四肢パターン形成 / 筋芽細胞 / 国際情報交換 / イギリス:アメリカ / Wnt-10a / βカテニン / 細胞接着 / EphA4 / AER / パターン形成 / Shh / FGF-4 / Hoxd13 / 四肢形成
Research Abstract

Expression of Shh and FGF4 is maintained in the limb bud through positive feedback induction, as indicated by ectodermal FGF4 expression by Shh protein applied to the anterior limb bud. We have shown here that FGF4 protein can also induce Shh and Hoxd13 expression in the hindlimb bud, but not in the forelimb bud, leading to respecification of the positional value.
Overexpression of Wnt10a normally expressed in the apical ectodermal ridge(AER) resulted in ectodermal expansion of FGF8 expression outside of the AER, through beta-catenin accumulation in the cellular fraction, as demonstrated by Western blotting.
Inhibition of cell sorting with PI-PLC and anti-EphA4 antibody suggests involvement of ephrin-A and EphA interaction during position dependent cartilage formation in the limb bud. Overexpression of ephrin-A2 that intensely expressed in the proximal limb bud can induce syndactyly and bifurcation of the phalangeal bones distally, where EphA4 is intensely expressed.
Overexpression of Wnt-inhibiting Sfrp3(Frzb1) or dominant-negative form of LEF1 maintains undifferentiated limb chondrocytes, whereas misexpression of Wnt8 or constitutive-active form of LEF1 promotes chondrocyte maturation and hypertrophy, leading to calcification of cartilage. Wnt5a, Wnt11,Wnt7a, and Wnt3a show region specific expression in the developing limb bud. Overexpression of these Wnts with RCAS affects myoblast proliferation and differentiation in the limb bud. Wnt5a promotes slow muscle fiber differentiation and inhibits fast muscle fiber differentiation. Dominant-negative form of Wnt11 has similar effect on muscle fibretype differentiation, which is reversed by wild-type Wnt11. Wnt-binding protein Sfrp2 is expressed in the myoblast progenitor cells and has inhibitory effect on muscle differentiaion upon misexpression.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (53 results)

All Other

All Publications (53 results)

  • [Publications] 泰江章博, 他: "骨格筋形成におけるマイオスタチンの役割"生体の科学. 52(4). 256-260 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kano, Y., et al.: "cAMP and calcium ionophore induce outgrowth of neuronal processes in PC12 mutant cells in which nerve growth factor-induced outgrowth of neuronal processes is impaired"Neuroscience Letters. 303(1). 21-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada, N., Nohno, T.: "Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4"Developmental Dynamics. 221(4). 402-411 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamagishi, T., et al.: "Expression of bone morphogenetic protein-5 gene during chick heart development : possible roles in valvuloseptal endocardial cushion formation"The Anatomical Record. 264(4). 313-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tokura, T., et al.: "Transdominant Negative FGF receptors inhibit proliferation of cultured glomerular mesangial cells"Kawasaki Medical Journal. 27(2). 43-51 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishi, M., et al.: "A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle"Biochemical and Biophysical Research Communications. 293(1). 247-251 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tao, H., et al.: "FGF10 is a mesenchymally derived stimulator for epidermal development in the chick embryonic skin"Mechanisms of Development. 116(1-2). 39-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kano, Y., et al.: "Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway"Neurochemical Research. 27(12). 1655-1661 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Church, V., et al.: "Wnt regulation of chondrocyte differentiation"Journal of Cell Science. 115(24). 4809-4818 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki, H., et al.: "Identification of cis-elements regulating expression of Fgf10 during limb development"International Journal of Developmental Biology. 46(7). 963-967 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., et al.: "The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis"Developmental Biology. 251(1). 142-156 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., et al.: "Dual roles of the WNT antagonist, Frzb-1 in cartilage development"Growth Plate. 54. 235-243 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hino, J., et al.: "Coordination of BMP-3b and cerberus is required for head formation of Xenopus embryos"Developmental Biology. 260(1). 138-157 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Anakwe, K., et al.: "Wnt signalling regulates myogenic differentiation in the developing avian wing"Development. 130(15). 3503-3514 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada, N., et al.: "Ephrin-A2 regulates position-specific cell affinity and is involved in cartilage morphogenesis in the chick limb bud"Developmental Biology. 264(2). 550-563 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hino, J., et al.: "Bone morphogenetic protein-3 family members and their biological functions"Frontiers in Bioscience. 9. 1520-1529 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamagishi, T., et al.: "Expression of Tbx20 RNA during chick heart development"Developmental Dynamics. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Galli, L.M., et al.: "A proliferative role for Wnt-3a in chick somites"Developmental Biology. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 岩本資己, 他(分担): "新・分子骨代謝学と骨粗鬆症(四肢形態形成と骨成長因子)"メディカルレビュー社. 13(263-275) (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 濃野 勉(分担): "骨形成・骨吸収の分子メカニズムと骨疾患:骨形成にかかわるWntシグナリング(米田俊之, 加藤茂明, 松本俊夫, 編)"羊土社. 8(53-60) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kano, Y., et al.: "cAMP and calcium ionophore induce outgrowth of neuronal processes in PC12 mutant cells in which nerve growth factor-induced outgrowth of neuronal processes is impaired."Neuroscience Letters. 303(1). 21-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada, N., et al.: "Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4."Developmental Dynamics. 221(4). 402-411 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamagishi, T., et al.: "Expression of bone morphogenetic protein-5 gene during chick heart development : possible roles in valvuloseptal endocardial cushion formation."The Anatomical Record. 264(4). 313-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tokura, T., et al.: "Transdominant negative FGF receptors inhibit proliferation of cultured glomerular mesangial cells."Kawasaki Medical Journal. 27(2). 43-51 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishi, M., et al.: "A missense mutant myostain causes hyperplasia without hypertrophy in the mouse muscle."Biochemical and Biophysical Research Communications. 293(1). 247-251 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tao, H., et al.: "FGF10 is a mesenchymally derived stimulator for epidermal development in the chick embryonic skin."Mechanisms of Development. 116(1-2). 39-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kano, Y., et al.: "Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway."Neurochemical Research. 27(12). 1655-1661 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Church, V., et al.: "Wnt regulation of chondrocyte differentiation."Journal of Cell Science. 115(24). 4809-4818 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki, H., et al.: "Identification of m-elements regulating expression of Fgf10 during limb development."International Journal of Developmental Biology. 46(7). 963-967 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., et al.: "The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis."Developmental Biology. 251(1). 142-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M., et al.: "Dual roles of the Wnt antagonist, Frzb-1 in cartilage development."Growth Plate. 54. 235-243 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hino, J., et al.: "Coordination of BMP-3b and cerberus is required for head formation of Xenopus embryos."Developmental Biology. 260(1). 138-157 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Anakwe, K., et al.: "Wnt signalling regulates myogenic differentiation in the developing avian wing."Development. 130(15). 3503-3514 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada, N., et al.: "Ephrin-A2 regulates position-specific cell affinity and is involved in cartilage morphogenesis in the chick limb bud."Developmental Biology. 264(2). 550-563 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hino, J., et al.: "Bone morphogenetic protein-3 family member and their biological functions."Frontiers in Bioscience. 9. 1520-1529 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamagishi, T., et al.: "Expression of Tbx20 RNA during chick heart development."Developmental Dynamics. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Galli, L.M., et al.: "A proliferative role for Wnt-3a in chick somites."Developmental Biology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Anakwe, K., et al.: "Wnt signalling regulates myogenic differentiation in the developing avian wing"Development. 130(15). 3503-3514 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hino, J., et al.: "Coordination of BMP-3b and cerberus is required for head formation of Xenopus embryos"Developmental Biology. 260(1). 138-157 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wada, N., et al.: "Ephrin-A2 regulates position-specific cell affinity and is involved in cartilage morphogenesis in the chick limb bud"Developmental Biology. 264(2). 552-565 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hino, J., et al.: "Bone morphogenetic protein-3 family members and thier biological functions"Frontiers in Bioscience. 9. 1520-1529 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamagishi, T., et al.: "Expression of Tbx20 RNA during chick heart development"Developmantal Dynamics. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Galli, L.M., et al.: "A proliferative role for Wnt-3a in chick somites"Developmental Biology. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishi, M., Yasue, A., Nishimatu, S., et al.: "A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle"Biochemical and Biophysical Research Communications. 293(1). 247-251 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tao, H., Yashimoto, Y., Yoshioka, H., et al.: "FGF10 is a mesenchymally derived stim zr epiulator for epidermal development in the chick embryonic skin"Mechanisms of Development. 116(1-2). 39-49 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto-Iwamoto, M., Kitagaki, J., et al.: "The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogensis"Developmental Biology. 251(1). 142-156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sasaki, H., Yamaoka, T., Ohuchi, H., et al.: "Identification of cis-elements regulating expression of Fgf10 during limb development"International Journal of Developmental Biology. 46(7). 963-967 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Church, V., Nohno, T., Linker, C., et al.: "Wnt regulation of chondrocyte differenitation"Journal of Cell Science. 115(24). 4809-4818 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 濃野 勉: "骨形成にかかわるWntシグナリング"実験医学. 20(17). 2469-2476 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasue, A., Tao, H., Nohno, T., et al.: "Cloning and expression of the chick p63 gene"Mechanisms of Development. 100. 105-108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kano, Y., Nohno, T., Takahashi, R., et al.: "cAMP and calcium jonophore induce outgrowth of neuronal processes in PC12 mutant cells in which nerve growth factor-induced outgrowth of neuronal processes is impaired"Neuroscience Letters. 303. 21-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wada, N., Nohno, T.: "Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4"Developmental Dynamics. 221. 402-411 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamagishi, T., Nakajima, Y., Nishimatsu, S., et al.: "Expression of bone morphogenetic protein-5 gene during chick heart development : possible roles in valvuloseptal endocardial cushion formation"Anatomical Record. 264. 313-316 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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